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Titolo:
[C-11,I-127] altropane: A highly selective ligand for PET imaging of dopamine transporter sites
Autore:
Fischman, AJ; Bonab, AA; Babich, JW; Livni, E; Alpert, NM; Meltzer, PC; Madras, BK;
Indirizzi:
Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA Massachusetts Gen Hosp Boston MA USA 02114 Nucl Med, Boston, MA 02114 USA Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 h Med, Dept Radiol, Boston, MA 02115 USA Organix Inc, Woburn, MA USA Organix Inc Woburn MA USAOrganix Inc, Woburn, MA USA Harvard Univ, Sch Med, Dept Psychiat, Div Neurochem,New England Reg Primate Res Ctr, Southborough, MA 01772 USA Harvard Univ Southborough MA USA 01772 es Ctr, Southborough, MA 01772 USA
Titolo Testata:
SYNAPSE
fascicolo: 4, volume: 39, anno: 2001,
pagine: 332 - 342
SICI:
0887-4476(20010315)39:4<332:[AAHSL>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; I-123 BETA-CIT; COCAINE RECOGNITION SITES; MONOAMINE REUPTAKE SITES; HEALTHY-HUMAN SUBJECTS; CFT WIN 35,428; LIVING HUMAN BRAIN; PARKINSONS-DISEASE; PRIMATE BRAIN; MONKEY BRAIN;
Keywords:
dopamine neurons; movement disorders; cocaine; Parkinson disease; SPECT imaging; WIN 35,428;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Fischman, AJ Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 32 Fruit St, Boston, MA02114 USA Massachusetts Gen Hosp 32 Fruit St Boston MA USA 02114 14 USA
Citazione:
A.J. Fischman et al., "[C-11,I-127] altropane: A highly selective ligand for PET imaging of dopamine transporter sites", SYNAPSE, 39(4), 2001, pp. 332-342

Abstract

The E isomer of I-123-2 beta -carbomethoxy-3 beta-(4-fluorophenyl)prop-1-en-3-yl)nortropane (Altropane(R)) shows high affinity (IC50 = 6.62 +/- 0.78 nmol) and selectivity (DA/5-HT = 25) for DAT sites in the striatum. Recently, dynamic SPECT studies in healthy volunteers and patients with Parkinson disease demonstrated that the kinetics of striatal accumulation followed a pattern that is characteristic of a reversible tracer with maximal accumulation within 30 min after injection. These findings suggested that radiolabeling Altropane with [C-11] might provide an equivalent and complementary tracer for PET studies. [I-127] Altropane was treated with HCl to hydrolyze the methyl ester bond and yield a precursor for [C-11] labeling. Introduction of an [C-11] methyl ester group was achieved by treatment with [C-11] CH3I followed by HPLC purification. Five healthy rhesus monkeys were injected with similar to 10 mCi of [I-127,C-11] Altropane and dynamic PET images were acquired over 90 min. Arterial blood samples were collected in parallel with imaging and metabolite analysis was performed by HPLC. The PET and metabolite corrected arterial blood data were to calculate k(3)/k(4) by two methods: 1) nonlinear least-squares fitting, and 2) a linear graphical method for reversible ligands. The synthetic procedure yielded high specific activity tracer, >1,000 mCi/mu mole, with radiochemical purity >95%. Synthesis time was similar to 30 min. The PET images revealed excellent striatal definition, with clear separation of caudate nucleus and putamen and minimal accumulation in brain regions with high 5HT transporter density. Metabolite analysis demonstrated that at 60 min after injection, similar to 80% of circulating tracer was intact [I-127,C-11] Altropane and the remainder was converted to polar metabolites. Values for k(3)/k(4) calculated by two analysis methods were remarkably similar: Method 1, 3.48 +/- 0.41; Method 2, 3.77 +/- 0.45 (mean +/- SEM, t = 2.31, df = 8, P = 0.64). These results establish that Altropane has the important characteristics of: 1) rapid and specific striatal binding; 2) high selectivity for DA vs. 5-HT transporter sites; 3)reversible binding kinetics; 4) potential for multiple injection studies; 5) high efficiency labeling with either [C-11] or [I-123]; 6) applicabilityfor both PET and SPECT. These properties make Altropane an important DAT ligand for both research and clinical applications. Synapse 39:332-342, 2001, (C) 2001 Wiley-Liss, Inc.

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Documento generato il 22/01/20 alle ore 06:57:03